Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are used for treating various depression and anxiety related disorders. Vortioxetine, also called Brintellix or Trintellix is a SSRI that is used for treating major depressive disorders. Vortioxetine can function as a serotonin modulator and stimulator, which can antagonize postsynaptic serotonin receptors and inhibit the reuptake of serotonin, and therefore can increase the availability of serotonin in the synaptic cleft and in the system. Patients with major depressive disorders who are treated with vortioxetine for a period of time may require that treatment with vortioxetine be replaced with treatment with monoamine oxidase inhibitors (MAOIs), which can also elevate the levels of serotonin. MAOIs can be used as the primary treatment if vortioxetine is not effective in certain patients.
However, when using vortioxetine, switching a patient to an MAOI may elevate the serotonin levels too much and may greatly increase the patient's risks of developing serotonin syndrome, or serotonin toxicity, for which there is no antidote, and which can be life threatening or fatal if not monitored carefully. Recent statistics from the Toxic Exposure Surveillance System (TESS) show that approximately 17% of the reported SSRI exposures result in moderate to severe outcomes, including 103 deaths in 2004 and 118 deaths in 2005. In some cases, the risks of transitioning from treatment with vortioxetine to an MAOI may be perceived as so severe that a physician may not even attempt treatment with vortioxetine in case a transition to treatment with an MAOI may be required.
Because there is no treatment available for serotonin syndrome, precautions for the transition from vortioxetine to MAOIs are especially important. According to the drug label for vortioxetine provided by the manufacturer, the recommendation washout period for patients who switch to MAOIs from vortioxetine is a wait of at least 21 days. However, this recommendation presumes that every patient requires the same washout period and may overlook that certain patient populations may require different washout periods when transitioning from vortioxetine to an MAOI.
The present applicants have discovered that certain patient populations or subpopulations are at higher risk of developing serotonin syndrome when transitioning from treatment with vortioxetine to MAOIs than was previously known, based on specific physiological characteristics, as described herein. The present disclosure describes new methods for addressing the risks of serotonin syndrome in such populations or subpopulations.